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Cell Rep. 2016 Mar 15;14(10):2426-39. doi: 10.1016/j.celrep.2016.02.040. Epub 2016 Mar 3.

Global Analysis of Cellular Protein Flux Quantifies the Selectivity of Basal Autophagy.

Author information

1
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
2
Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA; New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY 14203, USA.
3
Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14214, USA; New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY 14203, USA.
4
Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address: sghaemma@bio.rochester.edu.

Abstract

In eukaryotic cells, macroautophagy is a catabolic pathway implicated in the degradation of long-lived proteins and damaged organelles. Although it has been demonstrated that macroautophagy can selectively degrade specific targets, its contribution to the basal turnover of cellular proteins has not been quantified on proteome-wide scales. In this study, we created autophagy-deficient primary human fibroblasts and quantified the resulting changes in basal degradative flux by dynamic proteomics. Our results provide a global comparison of protein half-lives between wild-type and autophagy-deficient cells. The data indicate that in quiescent fibroblasts, macroautophagy contributes to the basal turnover of a substantial fraction of the proteome at varying levels. As contrasting examples, we demonstrate that the proteasome and CCT/TRiC chaperonin are robust substrates of basal autophagy, whereas the ribosome is largely protected under basal conditions. This selectivity may establish a proteostatic feedback mechanism that stabilizes the proteasome and CCT/TRiC when autophagy is inhibited.

PMID:
26947064
PMCID:
PMC5470642
DOI:
10.1016/j.celrep.2016.02.040
[Indexed for MEDLINE]
Free PMC Article

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